Phase 3
Completed N=673
Safety and Efficacy of a Switch to Doravirine, Tenofovir, Lamivudine (MK-1439A) in Human Immunodeficiency Virus (HIV-1)-Infected Participants Virologically Suppressed on an Anti-retroviral Regimen in Combination With Two Nucleoside Reverse Transcriptase Inhibitors (MK-1439A-024)
Source: ClinicalTrials.gov NCT02397096 ↗Enrolled (actual)
673
Serious AEs
4.4%
Results posted
Apr 2019
Primary outcomePrimary: Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL — 90.8; 94.6 Percentage of Participants
◆ Published Evidence
Established
94citations · ~13 / year
Switching to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains HIV-1 Virologic Suppression Through 48 Weeks: Results of the DRIVE-SHIFT Trial.
Summary
The multicenter, open label, randomized study will evaluate the safety and efficacy of a switch to MK-1439A (MK-1439 [doravirine] plus lamivudine and tenofovir disoproxil fumarate) in HIV-1-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to doravirine, tenofovir, lamivudine will be non-inferior to continuation of the regimen at Screening for 24 weeks, as assessed by the proportion of participants maintaining HIV-1 ribonucleic acid (RNA) <50 copies/mL. The Base Study results will be based on the first 48 weeks of this ongoing study.
Linked Publications (5)
-
Switching to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains HIV-1 Virologic Suppression Through 48 Weeks: Results of the DRIVE-SHIFT Trial.
-
Brief Report: Switching to DOR/3TC/TDF Maintains HIV-1 Virologic Suppression Through Week 144 in the DRIVE-SHIFT Trial.
-
Population Pharmacokinetic and Pharmacodynamic Analysis To Evaluate a Switch to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate in People Living with HIV-1.
-
Factors Associated With Weight Change After Continuing or Switching to a Doravirine-based Regimen.
-
Efficacy and Safety of Doravirine-based Regimens by Sex and Race: Long-term Results From Three Phase 3 Clinical Trials.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL |
90.8; 94.6 | — |
| SECONDARY Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) |
108.82; 109.00; -16.54; -1.94 | <0.0001 sig |
| SECONDARY Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C) |
139.14; 137.99; -24.74; -1.31 | <0.0001 sig |
| SECONDARY Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL |
93.7; 94.6 | — |
| SECONDARY Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts |
664.5; 655.6; 5.1; 18.0 | — |
| SECONDARY Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts |
664.5; 655.6; 5.1; 18.0 | — |
| SECONDARY Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL |
92.8; 93.3 | — |
| SECONDARY Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL |
92.8; 93.3 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA >=50 Copies/mL |
1.6; 1.8 | — |
| SECONDARY Percentage of Participants Experiencing ≥1 Adverse Event (AE) |
68.9; 52.5 | — |
| SECONDARY Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE) |
2.9; 3.6 | — |
| SECONDARY Percentage of Participants Discontinuing From Study Medication Due to an AE(s) |
2.5; 0.4 | — |
Eligibility Criteria
Inclusion Criteria
Inclusion Criteria include, but are not limited to:
- Have plasma Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) levels below the limit of quantification (BLoQ) ( = 6 months.
- Receiving first or second retroviral regimen (participants receiving a NNRTI at Screening must be on their first retroviral regimen)
- No history of using an experimental NNRTI
- Has a genotype prior to starting his/her initial antiretroviral regimen and no known resistance to any of the study agents
- Not receiving lipid lowering therapy or on a stable dose of lipid lowering therapy at the time of enrollment
- Has the following laboratory values at screening within 30 days prior to the treatment phase of this study: Alkaline phosphatase ≤ 3.0 x upper limit of normal (ULN), Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 5.0 x ULN, and Hemoglobin ≥9.0 g/dL (if female) or ≥10.0 g/dL (if male)
- Has a calculated creatinine clearance at the time of screening ≥ 50 mL/min, based on the Cockcroft-Gault equation
- Male or female participant not of reproductive potential or, if of reproductive potential, agrees to avoid becoming pregnant or impregnating a partner while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: 1) practice abstinence from heterosexual activity, or 2) use acceptable contraception during heterosexual activity
- For inclusion in Study Extension 1 (optional): completed the Week 48 visit; considered to have derived benefit from study participation up to Week 48; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug
- For inclusion in Study Extension 2 (optional): completed the Week 144 visit; considered to have derived benefit from study participation up to Week 144; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug
- For inclusion in Study Extension 3 (optional): completed the Week 240 visit; considered to have derived benefit from study participation up to Week 240; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug
Exclusion Criteria
Exclusion Criteria include, but are not limited to:
- Uses recreational or illicit drugs or has a recent history of drug or alcohol abuse or dependence
- Received treatment for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1 such as adefovir, emtricitabine, lamivudine, or tenofovir
- Has documented or known resistance to study drugs including doravirine, lamivudine, and/or tenofovir
- Participated in a study with an investigational compound or device within 30 days or anticipates doing so during the course of this study
- Used systemic immunosuppressive therapy or immune modulators within 30 days or anticipates needing them during the course of this study (short courses of corticosteroids will be allowed)
- Current, active diagnosis of acute hepatitis due to any cause (participants with chronic hepatitis B and C may enter the study as long as they fulfill all entry criteria, have stable liver function tests, and have no significant impairment of hepatic function)
- Has evidence of decompensated liver disease or has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte score >9
- Pregnant, breastfeeding, or expecting to conceive at any time during the study
- Female and is expecting to donate eggs or male and is expecting to donate sperm during the study
Data sourced from ClinicalTrials.gov (NCT02397096) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.